| Autor: |
Poulos, Michael G., Ramalingam, Pradeep, Winiarski, Agatha, Gutkin, Michael C., Katsnelson, Lizabeth, Carter, Cody, Pibouin-Fragner, Laurence, Eichmann, Anne, Thomas, Jean-Leon, Miquerol, Lucile, Butler, Jason M. |
| Předmět: |
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| Zdroj: |
Stem Cell Reviews & Reports; May2024, Vol. 20 Issue 4, p1135-1149, 15p |
| Abstrakt: |
In the adult bone marrow (BM), endothelial cells (ECs) are an integral component of the hematopoietic stem cell (HSC)-supportive niche, which modulates HSC activity by producing secreted and membrane-bound paracrine signals. Within the BM, distinct vascular arteriole, transitional, and sinusoidal EC subtypes display unique paracrine expression profiles and create anatomically-discrete microenvironments. However, the relative contributions of vascular endothelial subtypes in supporting hematopoiesis is unclear. Moreover, constitutive expression and off-target activity of currently available endothelial-specific and endothelial-subtype-specific murine cre lines potentially confound data analysis and interpretation. To address this, we describe two tamoxifen-inducible cre-expressing lines, Vegfr3-creERT2 and Cx40-creERT2, that efficiently label sinusoidal/transitional and arteriole endothelium respectively in adult marrow, without off-target activity in hematopoietic or perivascular cells. Utilizing an established mouse model in which cre-dependent recombination constitutively-activates MAPK signaling within adult endothelium, we identify arteriole ECs as the driver of MAPK-mediated hematopoietic dysfunction. These results define complementary tamoxifen-inducible creERT2-expressing mouse lines that label functionally-discrete and non-overlapping sinusoidal/transitional and arteriole EC populations in the adult BM, providing a robust toolset to investigate the differential contributions of vascular subtypes in maintaining hematopoietic homeostasis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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